Intestinal devices and methods for facilitating weight loss

ABSTRACT

Intestinal devices and methods for facilitating weight loss. In at least one embodiment of a method of patient treatment of the present disclosure, the method comprises the step of positioning a device, that is configured to reduce or limit localized intestinal distension, around a portion of an intestine of a patient.

PRIORITY

The present application is related to, claims the priority benefit of,and is a U.S. continuation application of, U.S. patent application Ser.No. 14/368,988, filed Jun. 26, 2014 and issued as U.S. Pat. No.9,820,879 on Nov. 21, 2017, which is related to, claims the prioritybenefit of, and is a U.S. § 371 National Stage Application of, PCTPatent Application Serial No. PCT/US2012/071560, filed Dec. 23, 2012,which is related to, and claims the priority benefit of, U.S.Provisional Patent Application Ser. No. 61/580,293 filed Dec. 26, 2011.The contents of each of the aforementioned patent applications arehereby incorporated by reference in their entirety into this disclosure.

BACKGROUND

Physical forces act on the intestinal wall when the intestine propelschime. The intestinal tract is abundantly innervated with mechanosensorsto sense the physical forces in intestinal wall when a meal transitsthrough the gut. The excitation of extrinsic sensory afferents providesclear evidence of the intestinal mechanosensory endings in response todistension. These sensory afferents respond to mechanical stimulationarising during intestinal distension and contraction. The level ofmesenteric afferent firing increases in proportion to the increase inintraintestinal pressure.

Brain-gut interactions are recognized as major players in physiologicaland pathpophysiological regulation of the intestinal tract. Theintestinal tract is dominated by enteric nervous system together withthe myogenic pacemakers known as interstitial cells of Cajal that allowsthe intestine to have a considerable degree of independent control fromthe central nervous system.

Although the mechanical sensory and afferent excitations in response tomechanical stimulation have been extensively studied, the role ofmechanical stimulation on intestinal contractility is poorly understood.Intestinal contractility consists of intricate interplay betweenintestinal sensors to afferent nerves to central nervous system and backto efferent nerves and intestinal smooth muscles.

Unfortunately, there is currently no quantitative method to study theintact (in vitro or in situ) intestinal contractility. To understand therelation between distension (intestinal sensors) and contractility(intestinal smooth muscles), a novel quantitative assay was used, namelyan in situ and in vitro isovolumic myograph, to determine the role ofextrinsic nervous system and intrinsic nervous regulation on thecontractility. An external restraint was used to inhibit the distensionand hence determine the role of distension or stretch. Depending on theoutcomes of the study, use of such a restraint may be useful to,depending on configuration and placement, operate as a safe andeffective weight loss device.

In view of the foregoing, a novel intestinal device and method for usingthe same to facilitate weight loss, for example, would be well acceptedin the marketplace.

BRIEF SUMMARY

In an exemplary method of patient treatment of the present disclosure,the method comprises the step of positioning a device that is configuredto reduce or limit localized intestinal distension, around a portion ofan intestine of a patient. In another exemplary method of patienttreatment of the present disclosure, the method comprises the step ofpositioning a device around a portion of an intestine of a patient. Inanother embodiment, the method is performed to facilitate weight loss ofthe patient. In yet another embodiment, the method is performed tofacilitate a reduction in food intake by the patient. In an additionalembodiment, the method is performed to treat obesity.

In an exemplary method of patient treatment of the present disclosure,the method is performed to treat a diabetic condition of the patient. Inan additional embodiment, the positioning step is performed to reduce orlimit localized distension of the intestine, slowing overall digestiveand/or excretory processes of the patient. In yet an additionalembodiment, the positioning step is performed to facilitate satiety ofthe patient. In another embodiment, the positioning step is performed toslow overall digestive and/or excretory processes of the patient.

In an exemplary method of patient treatment of the present disclosure,the method further comprises the step of introducing the device into thepatient prior to the step of positioning the device. In anotherembodiment, the introducing step is performed using a procedure selectedfrom the group consisting of a laparoscopic procedure and an opensurgical procedure. In yet another embodiment, the method furthercomprises the step of securing the device to the patient using one ormore sutures. In an additional embodiment, the method is performed totreat a blood glucose level condition of the patient.

In an exemplary method of patient treatment of the present disclosure,the positioning step is performed to position the device around at leasthalf of a perimeter of the intestine. In another embodiment, thepositioning step is performed to position the device around at leastthree quarters of a perimeter of the intestine. In yet anotherembodiment, the positioning step is performed to position the devicecompletely around the intestine. In an additional embodiment, the weightloss of the patient is facilitated by the patient eating less food. Inyet an additional embodiment, the weight loss of the patient isfacilitated by the patient eating less food due to slower overalldigesting and/or excretory processes of the patient.

In an exemplary method of patient treatment of the present disclosure,the device remains within the patient for a desired amount of time. Inan additional embodiment, the desired amount of time is selected fromthe group consisting of at least two weeks, between two weeks and onemonth, between one month and three months, between three months and sixmonths, between six months and one year, between one year and two years,and at least two years. In yet an additional embodiment, the methodfurther comprises the step of removing the device from the patient afterthe desired amount of time has elapsed. In another embodiment, thepositioning step is performed to position the device around a portion ofthe intestine at a first location. In yet another embodiment, the methodfurther comprises the step of positioning a second device configured toreduce or limit localized intestinal distension around a portion of theintestine at a second location.

In an exemplary method of patient treatment of the present disclosure,the device is positioned adjacent to the second device. In anotherembodiment, the device touches the second device. In yet anotherembodiment, the second device overlaps at least a portion of the device.In an additional embodiment, the device does not touch the seconddevice.

In an exemplary method of patient treatment of the present disclosure,the method further comprises the step of positioning a third deviceconfigured to reduce or limit localized intestinal distension around aportion of the intestine at a third location. In an additionalembodiment, the device touches at least one of the second device and thethird device. In yet an additional embodiment, the second deviceoverlaps at least a portion of the device, and wherein the third deviceoverlaps at least a portion of the second device. In another embodiment,the device, the second device, and the third device do not touch oneanother.

In an exemplary method of patient treatment of the present disclosure,the device comprises a temperature-sensitive material. In an additionalembodiment, the device changes from a first configuration to a secondconfiguration after introducing the device into the patient and prior tothe step of positioning the device. In yet an additional embodiment, thefirst configuration is compressed, and wherein the second configurationis uncompressed. In another embodiment, the introducing step isperformed by introducing at least part of a delivery device into thepatient, wherein at least a portion of the device is positioned withinthe delivery device.

In an exemplary method of patient treatment of the present disclosure,the introducing step further comprises the step of removing the devicefrom the delivery device. In another embodiment, the device is in afirst, compressed configuration when at least a portion of the device ispositioned within the delivery device, and wherein the device is in asecond, uncompressed configuration after the device is removed from thedelivery device. In yet another embodiment, the step of securing isperformed by placing the one or more sutures within one or more sutureapertures defined within the device. In an additional embodiment, thedevice comprises a flexible or pliable material.

In an exemplary device of the present disclosure, the device comprises abody configured for placement around a portion of an intestine of apatient and further configured to reduce or limit localized intestinaldistension. In another embodiment, the device comprises atemperature-sensitive material so that the device can change from afirst configuration to a second configuration after placement of thedevice within the patient. In yet another embodiment, one or more sutureapertures are defined within the body. In an additional embodiment, thedevice is configured to transform from a compressed, first configurationduring device delivery into the patient using a delivery device to anuncompressed, second configuration when the device is within the patientand outside of the delivery device.

In an exemplary device of the present disclosure, when the device ispositioned around the intestine, the device facilitates weight loss ofthe patient. In an additional embodiment, the weight loss of the patientis facilitated by the reduction or limitation of localized intestinaldistension, which slows overall digestive and/or excretory processes ofthe patient. In yet an additional embodiment, the weight loss of thepatient is facilitated by the patient eating less food due to a slowingof overall digestive and/or excretory processes of the patient. Inanother embodiment, when the device is positioned around the intestine,the device treats a diabetic or other blood glucose level condition ofthe patient.

In an exemplary device of the present disclosure, the body comprises aflexible or pliable material. In another embodiment, the body comprisesa biologically compatible polymer material. In yet another embodiment,the body further comprises a biologically compatible metal material. Inan additional embodiment, the body comprises a biologically compatiblemetal material. In yet an additional embodiment, the body has a first,open configuration that can transform to a second, closed or partiallyclosed configuration.

In an exemplary device of the present disclosure, the body defines afirst end and a second end. In an additional embodiment, engagement ofthe first end and the second end effectively closes the device. In yetan additional embodiment, the body is configured for placement around atleast half of a perimeter of the intestine. In another embodiment, thebody is configured for placement around at least three quarters of aperimeter of the intestine. In yet another embodiment, the body isconfigured for placement completely around the intestine.

In an exemplary device of the present disclosure, the device has aninner diameter and an outer diameter when in a closed or partiallyclosed configuration. In another embodiment, the device furthercomprises a hinged arm coupled to the body at a hinge location. In yetanother embodiment, wherein when a hinged arm end engages a relativebody end, the device is in a closed configuration. In an additionalembodiment, the device further comprises a post and a post aperturedefined within the body, the post configured to engage the post apertureto close the device. In yet an additional embodiment, the post islocated at or near a first end of the body, and the post aperture islocated at or near a second end of the body.

In an exemplary device of the present disclosure, a plurality of sutureapertures are defined within the body. In an additional embodiment, whena suture is positioned within suture apertures located at relativeopposing ends of the body, the device is in a closed configuration. Inyet an additional embodiment, the plurality of suture apertures allows auser of the device to adjust an overall closed configuration size of thedevice.

In an exemplary device of the present disclosure, the device furthercomprises one or more tabs positioned at or near a first end of thebody, and a tab receiver positioned at or near a second end of the body,the tab receiver configured to receive the one or more tabs to close thedevice. In another embodiment, the one or more tabs allow a user of thedevice to adjust an overall closed configuration size of the device. Inyet another embodiment, the device further comprises a second bodyconfigured for placement around a portion of the intestine of thepatient and further configured to reduce or limit localized intestinaldistension.

In an exemplary system of the present disclosure, the system comprises afirst intestinal device, comprising a body configured for placementaround a portion of an intestine of a patient and further configured toreduce or limit localized intestinal distension, and a delivery deviceconfigured to receive at least a portion of the first intestinal devicetherein and further configured for at least partial placement into thepatient to deliver the first intestinal device into the patient. Inanother embodiment, the system further comprises a second intestinaldevice, comprising a second body configured for placement around aportion of the intestine of the patient and further configured to reduceor limit localized intestinal distension. In yet another embodiment, thedelivery device is further configured to receive at least a portion ofthe second intestinal device therein and to deliver the secondintestinal device into the patient.

In an exemplary system of the present disclosure, the system comprises afirst intestinal device and a second intestinal device, each comprisinga body configured for placement around a portion of an intestine of apatient and further configured to reduce or limit localized intestinaldistension. In another embodiment, the system further comprises adelivery device configured to receive at least a portion of the firstintestinal device and the second intestinal device therein and furtherconfigured for at least partial placement into the patient to deliverthe first intestinal device and the second intestinal device into thepatient.

In an exemplary method of the present disclosure, the step ofpositioning the device is performed to position the device around theportion of the intestine selected from the group consisting of aduodenum, a jejunum, an ilium, and a large intestine. In anotherembodiment, the step of positioning the device is performed to positionthe device around a portion of a duodenum, and wherein the one or moresutures are attached to a stomach at or near a pyloric region. In yetanother embodiment, when the device is positioned around the portion ofthe intestine, the device does not constrict the intestine. In anadditional embodiment, when the device is positioned around the portionof the intestine, the intestine, when expanded due to digesting contenttherein, exerts a pressure against the device.

In an exemplary device of the present disclosure, the body is sized andshaped so not to invoke any stenosis of the intestine when placed arounda portion of the intestine. In an additional embodiment, the body issized and shaped so when the device is positioned around the portion ofthe intestine, the device does not constrict the intestine. In yet anadditional embodiment, the body, when in the second, closed or partiallyclosed configuration, defines an inner diameter that corresponds to anouter diameter of the intestine. In another embodiment, the body, whenin the second, closed or partially closed configuration, defines aninner diameter that is larger than an outer diameter of the intestine.

BRIEF DESCRIPTION OF THE DRAWINGS

The disclosed embodiments and other features, advantages, anddisclosures contained herein, and the matter of attaining them, willbecome apparent and the present disclosure will be better understood byreference to the following description of various exemplary embodimentsof the present disclosure taken in conjunction with the accompanyingdrawings, wherein:

FIGS. 1A and 1B show a device of the present disclosure in an open orpartially closed configuration, according to an exemplary embodiment ofthe present disclosure;

FIGS. 1C and 1D show a device of the present disclosure in a fullyclosed configuration, according to an exemplary embodiment of thepresent disclosure;

FIGS. 1E and 1F show a device of the present disclosure having a hingedportion, according to an exemplary embodiment of the present disclosure;

FIG. 1G shows a device of the present disclosure having a post anddefining a post aperture, according to an exemplary embodiment of thepresent disclosure;

FIG. 1H shows a device of the present disclosure having a series ofapertures defined therein in an open configuration, according to anexemplary embodiment of the present disclosure;

FIG. 1I shows a device of the present disclosure having a series ofapertures defined therein in a closed configuration, according to anexemplary embodiment of the present disclosure;

FIG. 1J shows a device of the present disclosure having a plurality oftabs and a tab receiver, according to an exemplary embodiment of thepresent disclosure;

FIG. 1K shows a device of the present disclosure positioned around atleast part of an intestine, according to an exemplary embodiment of thepresent disclosure;

FIG. 2 shows an exemplary myograph used to test an exemplary intestinaldevice, according to at least one embodiment of the present disclosure;

FIGS. 3A and 3B show data indicative of an increase in injection volumeduring pressurization of duodenum and colon, respectively, according tothe present disclosure;

FIGS. 3C and 3D show data indicative of an increase in diameter duringpressurization of duodenum and colon, respectively, according to thepresent disclosure;

FIGS. 3E and 3F show data indicative of an increase in compensationvolume rate during pressurization of duodenum and colon, respectively,according to the present disclosure;

FIGS. 4A and 4B show data indicative of temporal contractile waves ofthe duodenum and colon, according to the present disclosure;

FIGS. 5A and 5B show data indicative of the contractility of duodenumand colon vs. pressure relationship, respectively, according to thepresent disclosure;

FIGS. 5C and 5D show data indicative of the contractile tension ofduodenum and colon vs. diameter relationship, respectively, according tothe present disclosure;

FIGS. 6A-6D show data indicative of the relationship of duodenal andcolonic contractility (amplitude) and incremental stretch ratio duringpressurization, according to the present disclosure;

FIG. 7 shows use of a device around an intestine, according to anexemplary embodiment of the present disclosure;

FIGS. 8A-8C show data indicative of weight loss, food intake, andglucose levels, respectively, with and without use of a device in Wistarrats, according to the present disclosure;

FIGS. 9A-9C show data indicative of weight loss, food intake, andglucose levels, respectively, with and without use of a device in Zuckerdiabetic fatty rats, according to the present disclosure;

FIGS. 10A and 10B show block diagrams of systems, according to exemplaryembodiments of the present disclosure; and

FIG. 10C shows use of a device around a duodenum, according to anexemplary embodiment of the present disclosure.

An overview of the features, functions and/or configurations of thecomponents depicted in the various figures will now be presented. Itshould be appreciated that not all of the features of the components ofthe figures are necessarily described. Some of these non-discussedfeatures, such as various couplers, etc., as well as discussed featuresare inherent from the figures themselves. Other non-discussed featuresmay be inherent in component geometry and/or configuration.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

An exemplary device for placement around a portion of an intestine tofacilitate weight loss, to facilitate a reduction in food intake, totreat obesity, to treat a diabetic condition, to facilitate satiety,and/or to slow the overall digestive and/or excretory processes of apatient using the device of the present disclosure is shown in FIGS. 1Aand 1B. As shown in FIGS. 1A and 1B, an exemplary device 100 comprises abody 102 configured for placement around a portion of (at least part of)an intestine 208, as shown in FIG. 1K, for example. The overalldimensions of an exemplary device 100 of the present disclosure are suchto reduce/limit a localized intestinal expansion within a mammalian bodywhere device 100 is positioned.

Device 100, in at least one embodiment, comprises a flexible/pliablematerial (such as any number of biologically compatible polymers and/ormetals) that, when configured as a device 100 of the present disclosure,can fit around part of an intestine 208 and limit intestinal distension.As shown in FIGS. 1A and 1B, device 100 is in an open configuration, andas shown in FIGS. 1C and 1D, device 100 is in a fully closedconfiguration. Other embodiments of devices 100 of the presentdisclosure may have a partially closed configuration resembling toconfigurations shown in FIGS. 1A and 1B. However, and in variousembodiments of devices 100 of the present disclosure, devices 100 mayremain in an open configuration, and may never form a fully closedconfiguration, when positioned around at least part of an intestine 208,such as around most or a majority of a perimeter of an intestine 208. Adevice first end 104 and a device second end 106, as shown in FIGS. 1Aand 1B, may engage one another upon closure of device 100, as shown inFIGS. 1C and 1D, or may be in close proximity to one another when device100 is positioned around an intestine 208. One or more suture apertures108, as shown in FIGS. 1A and 1C, may be defined within body 102 so thatwhen device 100 is positioned around an intestine 208, sutures 144(shown in FIG. 1I, such as silk sutures) may be used to secure device100 around the intestine 208 to prevent device migration. In lieu ofsuture apertures 108, for example, one or more sutures 144 could be usedand placed directly through and/or around portions of device 100.

An exemplary device 100 of the present disclosure has a length 110 (asshown in FIG. 1C) and an inner diameter 112 and an outer diameter 114(as shown in FIG. 1D) when positioned around at least a portion of anintestine 208. In an open configuration, as shown in FIGS. 1A and 1B,the inner diameter 112 and outer diameter 114 (assuming a full circle)would be relatively larger than the inner diameter 112 and the outerdiameter 114 of the same device in a closed or partially closedconfiguration. Other embodiments, as referenced in detail herein, maynot have a relative inner diameter 112 or outer diameter 114 when notpositioned around an intestine 208, but would have said diameters whenpositioned around at least a portion of an intestine 208. In addition,and as shown in FIG. 1D, device 100 has at least one inherent thickness116, which may vary from embodiment to embodiment. Various device 100embodiments can be configured as bands, sleeves, or cuffs, for example.

An additional embodiment of a device 100 of the present disclosure isshown in FIGS. 1E and 1F. As shown therein, device 100 comprises ahinged arm 118 connecting to part of body 102 at a hinge location 120.Hinged arm 118 is shown as being relatively open in FIGS. 1E and 1F, andwould, in at least one embodiment, fully close so that a hinged arm end122 would contact second end 106 of body 102. In other embodiments (notshown), hinged arm 118 would close but the entirety of device 100 maynot actually close (such that first end 104 does not contact and/oroverlap second end 106).

Additional device embodiments are shown in FIGS. 1G-1J. As shown in FIG.1G, an exemplary device 100 may comprise a post 140 and define one ormore post apertures 142, wherein when post 140 is positioned within postaperture 142, device 100 is secured in a closed configuration, around anintestine 208 if desired. In at least one embodiment, post 140 is at ornear a first end 104 of the device, and post aperture 142 is located ator near a second end 106 of the device 100. FIGS. 1H and 1I show device100 embodiments where two apertures 108 defined therein may be used tosecure the device together using one or more sutures 144 as shown inFIG. 1I. FIG. 1H shows an exemplary device 100 in an open configuration,while FIG. 1I shows the same device 100 in a closed configuration with asuture 144 positioned through one or more suture apertures 108. Such anembodiment, having a plurality of apertures 108 defined therein, wouldallow a user positioning such a device 100 to be able to adjust theoverall inner diameter 112 of the device 100 when positioning the samearound an intestine 208.

An additional embodiment of a device 100 of the present disclosure isshown in FIG. 1J, whereby device 100 comprises one or more tabs 146configured to fit within an aperture 147 of tab receiver 148, so thatwhen a tab 146 is positioned within aperture 147 of tab receiver 148,tab receiver 148 holds that part of device 100 in place by way of tab146. In at least one embodiment, the tabs 146 are at or near a first end104 of the device, and the tab receiver 148 is located at or near asecond end 106 of the device 100. Such an embodiment, having a pluralityof tabs 146, would allow a user positioning such a device 100 to be ableto adjust the overall inner diameter 112 of the device 100 whenpositioning the same around an intestine 208.

FIG. 1K shows an exemplary device 100 of the present disclosurepositioned around at least part of an intestine 208. As shown therein,device 100 may be secured in place using one or more sutures 144 throughapertures 108 and through part of a wall of intestine 208 to preventdevice 100 migration. Removal of an exemplary device 100, in variousembodiments, may be by way of removing sutures 144, disengaging post 140from post aperture 142, removing tab 146 from tab receiver 148, etc., orby generally opening the device from a fully closed or partially closedconfiguration to a relatively open configuration. As noted in furtherdetail below and shown in FIG. 7, two or more devices 100 can be placedin parallel (adjacent to one another (with or without spaces in between)or at least partially overlapping one another) to cover a larger portionof an intestine 208.

Placement of various device 100 embodiments of the present disclosurearound an intestine 208 may occur at various intestinal locations. Thehuman small intestine, for example, extends from the pyloric region ofthe stomach and forms, from proximal end to the distal end, theduodenum, the jejunum, and the ilium, the latter of which is immediatelyadjacent to the proximal end of the large intestine. In at least onemethod of using a device 100 of the present disclosure, and as discussedin further detail herein, device 100 can be placed around the duodenum.FIG. 10C shows a portion of a mammalian digestive system 150, includingthe stomach 152, the pyloric region 154 of the stomach 152, and variousintestine 208 portions, including the duodenum 156, the jejunum 158, theilium 160, as well as the large intestine 162. As shown therein, anexemplary device 100 of the present disclosure is positioned around atleast a portion of intestine 208, namely at duodenum 156, and is securedto stomach 152 at or near pyloric region 154 using one or more sutures144. Placement of various device 100 embodiments may be made at one ormore of the other above-referenced portions of intestine 208. As shownin FIG. 7, for example, three devices 100 can be used and positionedrelative to one another at the duodenum 156.

Various device 100 embodiments of the present disclosure, which may alsobe referred to as non-constrictive cuffs (NCCs), may be made ofpolytetrafluoroethylene (PTFE), silicone rubber, or a bioabsorbablepermeable or non-permeable material, for example. Such materials, andother biologically-compatible materials, would be sufficiently hard asto bear the forces generated from duodenal motility and distension butflexible enough to be configured to wrap around the duodenum 156 so thatdevice 100 would be generally cylindrical.

FIG. 7 shows an exemplary embodiment of a device 100 of the presentdisclosure being delivered and positioned about an intestine 208. Asshown in FIG. 7, an exemplary delivery device 700, which may be ageneral catheter, a delivery catheter, trocar, another type of tube, ora component having a lumen 702 defined therein, can be deliveredlaparoscopically, for example, into the patient so that a device 100positioned therein can ultimately be delivered into the patient. Invarious embodiments, device 100 can have a first configuration 704, suchas a folded, curled, or other configuration that is intended tofacilitate delivery, and can have a second configuration 706, also asshown in FIG. 7, that is suitable for positioned about an intestine 208.First configuration 704, in various device 100 embodiments, may be therelatively open configuration, and second configuration 706 may be thepartially or fully closed configuration. As shown in FIG. 7, anexemplary device 100 of the present disclosure has a relatively curledfirst configuration 704 that can open to an intermediate configuration705 at a first temperature, and can ultimately change to a secondconfiguration 706 at or near a second temperature. In at least oneembodiment, the first temperature would be at or near room temperature(less than body temperature), and the second temperature would be at ornear body temperature. To facilitate the change in configuration,temperature-sensitive materials such as nitinol can be used to compriseat least part of device 100, and devices 100 can be generally configuredto have a first configuration 704 and a second configuration 706suitable for delivery and placement, respectively. Materials comprisingdevice 100, in such an embodiment, give device 100 a “memory”characteristic, such as changing from a first configuration 704 to asecond configuration 706, whereby the second configuration 706 is anatural configuration at or near body temperature based upon the memorycharacteristic. Aside from temperature-sensitive materials, othermaterials that would allow device 100 to have a memory characteristic,such as a native partially or fully closed configuration, but alsopliable/flexible enough to open, fold, or curl, for example, tofacilitate delivery, may be used as well.

In various embodiments, the cross-section of device 100, such as shownin FIGS. 1B, 1D, and 7, may be generally circular or elliptical to fitthe duodenal contour, whereby the longitudinal configuration of device100 mimics the duodenal axial contour. In various embodiments, the innerdiameter 114 of device 100, as shown in FIG. 1D, may be 105% to 150% ofthe duodenal external diameter. Furthermore, and in various embodiments,the length 110 of device 100, as shown in FIG. 1C, may vary from 10% to80% of the entire length of duodenum 156, or may be even smaller (lessthan 10%), as shown in the general ring embodiment shown in FIG. 1C.

As shown in FIG. 7, and in various embodiments of devices 100 of thepresent disclosure, device 100 can be first collapsed (in a firstconfiguration 704) to fit through standard trocar (an exemplary deliverydevice 100), and once in the abdomen, device 100 can be opened to sectorfor implantation and then folded back for wrapping the duodenum 156.When implanted, and in at least one embodiment of a method of using adevice 100 of the present disclosure, device 100 will be first opened tosector and slipped half underneath the duodenum 156 from non-mesentericside and then folded to wrap the duodenum 156. An axial gap 708 (0.6 to2 mm, for example), in at least some device 100 embodiments, is made ondevice 100 to prevent disturbances to the mesentery 710 circulation ofthe bowel. Gap 708, also referred to as a lateral opening, on device 100allows mesentery 710 access the duodenum 156 without compression toprevent ischemia. In at least some embodiments, and as shown in FIG. 7,an angle (θ) of our about 30° to 45° can be formed within device 100 tocreate gap 708, noting that smaller or larger gaps 708 may be used aswell.

One or more sutures 144, such as shown in FIGS. 1K and 7 and asreferenced above, may be used to secure an end of the device 100 (suchas a proximal end) or another portion of device 100 on the stomach 152at or near the pyloric sphincter to prevent device 100 migration.Additional sutures 144 may be made be placed axially along device 100 atthe two edges of the sector with care to not close the sector to furtherreinforce the stiffness of device 100 during distension. Sutures 144,when placed as such, will penetrate the mesentery and stabilize device100 in place during motility.

As shown in FIG. 7, more than one device 100 can be positionedabout/upon intestine 208, either immediately adjacent to each other,with gaps in between, or overlapping one another. Based on thedimensions of intestine 208 at a particular location, said multipledevices 100 can be of different sizes (having different lengths 110and/or diameters 112). Regarding device 100 sizes, preferred embodimentsof the present disclosure are sized and shaped so not to invoke anyintestine 208 stenosis. For example, and in various device 100embodiments of the present disclosure, when devices 100 are in a fullyor partially closed configuration around part or all of an intestine208, device 100 does not constrict intestine 208, as the dimensions ofdevice 100 exceed the native dimensions (perimeter, diameter,circumference, etc.) of intestine 208. For example, if a portion of asmall intestine (such as duodenum 156) has an outer diameter of 5.0 cm,and it is desired to position an exemplary device 100 at that portion ofduodenum 156, the dimensions of device 100 would be such that whendevice 100 is positioned around some or all of duodenum 156 at thatportion/location, the effective inner diameter 112 of device 100 isgreater than 5.0 cm. Devices 100 of the present disclosure, alsoreferred to as non-constrictive cuffs as referenced above, areconfigured to avoid constricting intestine 208, but are configured, asnoted above, to provide a restriction of intestine 208 beyond the normalnon-distended intestional dimensions. Accordingly, and in various device100 embodiments of the present disclosure, inner diameter 112 of device100, when in a partially or fully closed configuration, is greater thanan outer diameter of intestine 208 at the location of placement ofdevice 100 thereon. In at least various other device 100 embodiments,inner diameter 112 of device 100, when in a partially or fully closedconfiguration, is no less than the outer diameter of intestine 208 atthe location of placement of device 100 thereon.

Various devices 100 of the present disclosure may be used to facilitateweight loss, or for other purposes as referenced herein, as follows. Inat least one embodiment of a method of using such a device 100, themethod comprises the step of delivering a device 100 laparoscopically(for example) into a patient relative to the patient's intestine 208.The device 100 may then be positioned around a patient's intestine 208and secured in place using one or more closure mechanisms describedherein and one or more sutures 144 if desired. Additional devices 100may be delivered in a similar fashion if desired. In at least oneembodiment of a method of the present disclosure, the device 100 may bedelivered through an open surgical procedure. The device 100 may then beleft in place for a desired amount of time, and ultimately removed byreversing the procedure (entering the patient, removing the device 100,and withdrawing the device 100 from the patient).

As described in detail below, use of such a device 100 can significantlyattenuate the intestinal contractility in response to an increase inintraluminal pressure. Such a decrease in contractility has the effectof slowing the movement of food through a patient's gut during thedigestion and excretion processes. Such a slowing of said processes, byway of contractility attenuation using a device of the presentdisclosure, would cause a patient to ultimately ingest less food, andtherefore lose weight while the device 100 is positioned at leastpartially around the patient's intestine 208.

An exemplary device 100 of the present disclosure was tested using mouseintestine with an exemplary myograph as shown in FIG. 2 and referencedin further detail below. Other myograph embodiments, such as thosedisclosed within U.S. Patent Application Publication No. 2010/0022265 ofKassab and Lu, may also be used to perform the tests described below.

FIG. 2 shows an exemplary system (myograph) 200, such as the myographused in the present study, and the in situlin vitro experimental setup,used in the present study. As shown in FIG. 2, system 200 comprises achamber 202 with a catheter 204 on one side wall of the chamber 202which bridges the lumen 206 of an intestine 208 to an inflation flask210 and pressure transducer 212. A 50 ml inflation flask 210 with PSS214 (connected to a pressure regulator 216) inflated the intestine 208to the desired pressure. The catheter 204, a solid state pressuretransducer 212 (SPR-524, Microtip catherter transducer, Millar Inc,Texas), a tube 218 to the inflation flask 210, and a compensatorymicrosyringe 220 were assembled using a connector 222. The clamping oftube 218 between inflation flask 210 and intestine 208, by way of clamp224, achieved isovolumic conditions, i.e., the intestinal lumen volumewas constant.

The compensatory microsyringe 220 (50 μl gastight microsyringe,UltraMicroPump III, and Micro 4™ microsyringe controll, World PrecisionInstruments, USA) was used to stablize (maintain) the baseline pressuresince water transport across the intestinal wall changes theintraluminal pressure. The criteria for compensation was to mantain thecontour of periodic pressure at baseline. The rate of compensationgenerally changed with inflation pressure. A CCD camera on a microscopeand an image proccessing system tracked the intestinal diameter. As theintestine was inflated to a desired pressure (e.g., 5 mmHg, 10 mmHg,etc.), the clamp 224 was closed, and the intestinal contraction orrelaxation was quantified by the variation of intraluminal pressureunder a constant rate of compensation. The isovolumic system 200recorded the periodic contractions of intestine in response to changesof inflation pressure. The isovolumic measurements usually lasted 5 to10 minutes and the intestine 208 was reversed to proximal and distalopen as in physiological state.

The animal experiments were performed as follows. Twelve C57BL/6J miceat 24 weeks of age, having 31.2±5.8 grams of body weight, were obtainedfrom Jackson Laboratory. The animals were acclimated to the facility forapproximately one (1) week prior to the start of the study. The animalswere anesthetized with xylazine (1 mg/kg, i.p.) and ketamine (9 mg/kg,i.p.) and maintained with xylazine (0.5 mg/kg) and ketamine (4.5 mg/kg)every half hour. The animal experiments were performed in accordancewith the guidelines of Institute of Laboratory Animal Research Guide,Public Health Service Policy, Animal Welfare Act, and an approved IACUCprotocol.

In situ intestinal contractility. Under anesthesia, the abdominal skinand muscle layers of the animal were opened to expose either theduodenum or the distal colon. The intestine was moistened with warm (37°C.) HEPES physiological saline solution (HEPES-PSS in mmole/L: 119 NaCl,4.7 KCl, 3 HEPES acid, 2.3 HEPES sodium salt, 1.17 MgSO₄, 1.6 CaCl, 5.5Dextrose). The applied PSS was aerated with 95% O₂ and 5% CO₂. Theintestine was cannulated with a HEPES-PSS prefilled catheter (ID: 1 mm,OD: 2 mm) which connected to the isovolumic system 200 as shown in FIG.2. A 2 mm incision was cut at the oral intestine where the catheter 204(having an outer diameter of 2 mm) was inserted into the intestinallumen. The incision was tied on the catheter 204 with 6-0 silk suturetwice to ensure no leakage. Two milliliters of PSS was gently injectedinto the intestine through the catheter 204 to wash away the content.Another 6-0 silk suture was tied 11 mm away towards the anal intestinefrom the cannulation. The intestinal mesentery was untouched to allowthe intestine to work in a physiological environment maintaining normalcirculation and vagal responses.

In vitro intestinal contractility. The animals were euthanized byoveranesthesia. Deudenum or distal colon was excised quickly and placedin ice cold (4° C.) PSS to slow down cellular metabolism and preservecell vitality during preparation. The adjacent tissue was dissected withthe aid of a stereo microscope. The intestine was allowed to warm up toroom temperature (22° C.) slowly over approximately 10-15 minutes andwas transferred to a chamber 202 of the isovolumic myograph 200 withHEPES-PSS (22° C.). The two ends of the intestine were cannulated toconnectors 226, 228 (having an inner diameter of 1 mm and an outerdiameter of 2 mm) in the chamber 202 of the isovolumic myograph 200 andthe length of the intestine considered was 11 mm. The content in theintestine was gently rinsed with HEPES-PSS. The intestine in the chamber202 was slowly warmed to 37° C. over approximately 15-20 minutes andequilibrated for 30 minutes at a basal pressure of about 1 mmHg beforedistension.

Intestinal contractility and inflation pressure. The mechanicalstimulation of intestine was induced by random sequence of intraluminalinflation pressures. The intestinal contraction was quantified by theintraluminal pressure under isovolumic condition and the contractilitywas characterized with the amplitude and period of the pressurewaveforms. The intestine was inflated to a desired pressure by apressure regulator 216 connected to flask 210 as referenced above. Theclamping of the tube 222 between the inflation flask 210 and theintestine 208 maintained a constant volume of solution in the intestinallumen (an isovolumic condition). The compensatory microsyringe 220maintains isovolumic conditions at, for example, an infusion rate of0.6-2.3 μl/min. The data was discarded if the rate was larger than 5μl/min since this implied damage (leakage) of the intestinal wall. Atisovolumic conditions, the variations of intraluminal pressure wererecorded with a data acquisition system (Biopac, MP100, Houston, Tex.).The amplitude, frequency, and contractile duration of pressure waveformswere analyzed to characterize the intestinal contractility.

Intestinal restraint: A loosely fitting restraint (an exemplary device100 of the present disclosure) made of plastic tube (body 102) was usedto determine the role of stretch. A portion of body 102 was removed(semi-cylinder) to allow the intestinal mesentery to pass throughfreely. The dimensions of body 102 used in the study were 12.5 mm inlength, 6 mm in internal diameter, and 2 mm in wall thickness, notingthat bodies 102 of different dimensions may also be used in similarstudies. The width of the semi-cylinder was about 0.3 mm. Thesemi-cylinder was axially opened up to a sector with the aid of aforceps. The semi-cylinder was passed through the intestine. The forcepswas released to allow the semi-cylinder to fully wrap the intestine. Thesemi-cylinder was circumferentially tied with a 6-0 silk suture torestrain the intestine into the lumen of the semi-cylinder when theintesine was inflated. Device 100 covered the cylindrical area andlimited the stretch of intestinal circumference despite an increase inintraluminal pressure in the intestine. The noncovered intestinal wallon the two ends was distended during the increase in intraluminalpressure. To verify that the duodenal nerves were not damaged whilemounting the restraint, the contractility was measured again afterremoval of device 100.

Protocol of mechanical stimulation. The intraluminal pressure wasincreased stepwise to 2, 5, 10, 15, 20, 30, 40, and 50 (colon only) mmHgby injection of HEPES PSS into the intestine at rate of 0.05 ml/min,respectively. The intestinal contraction at isovolumic condition wasrecorded by the changes of pressure at each inflation or distensionpressure. This protocol was applied to both in situ and in vitrointestine with or without intestinal restraint. In the experiment of invitro intestine, acetylcholine (10⁻⁶ mole/l) was used to elicitnon-neuroactive contraction of intestinal smooth muscle at intraluminalpressure of 40 mmHg (duodenum) or 50 mmHg (colon) to evalutecontractility of intestinal smooth muscle.

Data Analysis and Statistics. The intestinal contractile amplitude wasrepresented by the amplitude of pressure variation. The incrementalstretch ratios of intestinal circumference during the stepwise inflationwere computed with and without device 100. The contractile tension wascalculated by the amplitude of pressure multiplied by the intestinaldiameter. The linear regression of intestinal contractility andincremental stretch was then analyzed. The data were presented as mean±SD and significant differences between groups were determined bystudent t-test. Significant differences between the in situ, in vitro,and restraint groups were determined by use of Analysis Of Variance(ANOVA) between groups. A probability of p<0.05 was consideredindicative of a statistically significant difference.

Results. The injection volumes into duodenum and colon for both in situand in vitro inflation were summarized in FIGS. 3A and 3B, respectively,which increased rapidly during low pressure and slowed down during highpressure. Changes of injection volume, diameter, and compensation rateduring pressurization of duodenum (left column) and colon (right column)are generally shown in FIGS. 3A-3F. FIGS. 3A and 3B show an increase ininjection volume during pressurization of duodenum and colon,respectively. Inflation volume was significantly smaller when restraintapplied. FIGS. 3C and 3D show an increase in diameter duringpressurization of duodenum and colon, respectively. Diameter did notchange when restraint was applied. FIGS. 3E and 3F show an increase incompensation volume rate during pressurization of duodenum and colon,respectively. Compensation rate was suppressed by restraint. There wereno difference between in situ and in vitro states (p>0.05), and therestraint significantly reduced the injection volume, diameters, andcompensation rate at in situ and in vitro states (p<0.05). As shownwithin the figures, ⋄ indicated an in situ state, ♦ indicates an in situstate with a restraint, Δ indicates an in vitro state, and ▴ indicatesan in vitro state with a restraint.

As shown in the figures, the diameters had a similar trend to theinjection volume (FIGS. 3C and 3D), which reflect the circumferentialdistensibility of the duodenum and colon during pressurization. Thecompensatory rates of duodenum and colon at isovolumic conditionincreased rapidly during low pressure and slowed down during highpressure (FIGS. 3E and 3F, respectively). The compensatory rates,diameters, and compensatory rates were not significantly differentbetween in situ and in vitro inflation (p>0.05). The application of therestraint (an exemplary device 100 of the present disclosure) on theduodenum or colon limited the increase of in situ and in vitro injectionvolume, diameters, and compensatory rates during pressurization, asshown in FIGS. 3A-3F.

The typical intraluminal pressure waveforms produced by contraction ofduodenum and colon are shown in FIGS. 4A-4F in which the amplitude ofintraluminal pressure was affected by changes in inflation pressure.FIGS. 4A-4F generally show typical in situ and in vitro temporalcontractile pressure waves of duodenum (left column) and colon (rightcolumn) at various inflation pressures. As shown in FIGS. 4A and 4B, andwithout restraint, the in situ contractile pressure waves of duodenumand colon were significant. As shown in FIGS. 4C and 4D, also withoutrestraint, the in vitro contractile pressure waves of duodenum and colonwere significantly attenuated in comparison with in situ state. When arestraint was applied, as shown in FIGS. 4E and 4F, the in situcontractile pressure waves of duodenum and colon were significantlyattenuated. The amplitude reached a maximum under all conditions at 5mmHg of inflation pressure and decreased monotonically with furtherincrease of inflation pressure. The in vitro contraction of colon wassignificantly attenuated as shown in FIG. 4D.

As generally shown in FIGS. 5A-5D, the contractility of duodenum (leftcolumn) and colon (right column) as a function of pressure or diameter.FIGS. 5A and 5B show the contractility of duodenum and colon vs.pressure relationship, respectively, whereby the restraint significantlyreduced the contractility of duodenum and colon at in situ and in vitrostates (p<0.05). FIGS. 5C and 5D show the contractile tension ofduodenum and colon vs. diameter relationship, respectively, whereby therestraint significantly reduced the contractile tension of duodenum andcolon at in situ and in vitro states (p<0.05). As shown within thefigures, ⋄ indicated an in situ state, ♦ indicates an in situ state witha restraint, Δ indicates an in vitro state, and ▴ indicates an in vitrostate with a restraint.

The contractility of duodenum and colon are shown as a function ofinflation pressure in FIGS. 5A and 5B, respectively. The in situcontractility of duodenum increased from 0.97±0.29 to 1.42±0.39 mmHgwhen the inflation pressure was increased from 1 to 5 mmHg. The duodenalcontractility then decreased significantly down to 0.4±0.28 mmHg whenthe inflation pressure was further increased from 5 to 40 mmHg as shownin FIG. 5A. The in situ contractility of colon increased from 4.15±1.16to 4.86±1.32 mmHg when the inflation pressure increased from 1 to 5mmHg. The colonic contractility, then, decreased significantly down to1.61±0.98 mmHg when the inflation pressure was further increased from 5to 50 mmHg as shown in FIG. 5B. The restraint did not affect the in situduodenal contractility at lower inflation pressures (<5 mmHg), butattenuated the contractility when the inflation pressures were >10 mmHgas shown in FIG. 5A. However, the restraint largely attenuated the insitu colonic contractility in the entire range of inflation pressures asshown in FIG. 5B. The in vitro contractility of duodenum linearlydecreased with increase in inflation pressure and was significantlyattenuated in comparison with the in situ contractility as shown in FIG.5A. The in vitro contractility of colon was significantly attenuated incomparison with the in situ contractility as shown in FIG. 5B. Thepresence of the restraint essentially abolished the in vitrocontractility of duodenum and colon in the entire range of inflationpressures (shown in FIGS. 5A and 5B, respectively).

The in vitro smooth muscle contraction of duodenum and colon stimulatedby ACh, however, was still similar to maximum contractility at the insitu state. The contractility of duodenum and colon recovered 95-100%when the restraint was removed, which confirms that the application ofin situ restraint did not damage the nerve fibers or vasculature ofduodenum and colon. The relationship between contractile tension anddiameter of duodenum and colon were analyzed in FIGS. 5C and 5D,respectively. There was significant peak of contractile tension in bothin situ and in vitro preparations, which implicates duodenal and colonicsmooth muscle appears similar to skeletal and cardiac muscle whichgenerates the maximal tension at an optimal length. The restraint wassmaller than the optimal length and hence significantly attenuated thecontraction of duodenum and colon.

FIGS. 6A-6D generally show the relationship of duodenal and coloniccontractility (amplitude) and incremental stretch ratio duringpressurization. FIG. 6A is indicative of the duodenum inflated withoutrestraint, and in FIG. 6B, the duodenum was restrained while inflated.Linear regression showed an excellent linear relationship in FIG. 6A butnot in 6B. FIG. 6C is indicative of the colon inflated withoutrestraint, and in FIG. 6D, the colon was restrained while inflated.Linear regression showed an excellent linear relationship in FIG. 6C butnot in 6D. A linear regression of intestinal contractility andincremental strain suggests a direct correlation of circumferentiallyincremental strain and contractility (shown in FIGS. 6A and 6B) of invitro and in situ duodenum and colon (shown in Table 1, below, whereinR²>0.9).

TABLE 1 The slope, intercept, and R² of linear regression byleast-squares fit Slope Intercept R² P value Duodenum: In vivo 4.62 ±1.03 0.42 ± 0.11   0.933 ± 0.311 0.047-0.012 Ex vivo 4.55 ± 1.16 0.14 ±0.08   0.985 ± 0.32* 0.041-0.009 In vivo 3.12 ± 1.36 0.41 ± 0.29^(†)0.523 ± 0.28 0.095-0.053 restraint Ex vivo 2.72 ± 1.31 0.23 ± 0.21^(‡)0.376 ± 0.22 0.169-0.073 restraint Colon: In vivo 11.0 ± 2.08 1.31 ±0.29  0.953 ± 0.33 0.043-0.011 Ex vivo 6.80 ± 1.71  0.89 ± 0.15*  0.916± 0.32* 0.049-0.019 In vivo 8.16 ± 2.96 1.39 ± 0.73^(†) 0.697 ± 0.250.093-0.049 restraint Ex vivo 4.73 ± 2.64 0.41 ± 0.39^(‡)  0.579 ±0.21^(‡) 0.096-0.049 restraint Notes: *P < 0.05 indicates statisticaldifference between “ex vivo” and “in vivo”. ^(†)P < 0.05 indicatesstatistical difference between “in vivo restraint” and “in vivo”. ^(‡)P< 0.05 indicates statistical difference between “ex vivo restraint” and“ex vivo”.

The intercept of linear regression, which reflects the offset of thecontractility response to stretch stimulation, significantly shifteddownward in in vitro duodenum and colon as shown in Table 1. The slope,which reflects the amplification of the contractility response tostretch stimulation, significantly decreased in in vitro colon but didnot change among in situ duodenum. With the restraint (an exemplarydevice 100), the R² of linear regression decreased significantly in bothin vitro and in situ intestines and became statisticallynon-significant. FIGS. 6C and 6D show that the intestinal contractilityresponse to incremental strain is blunted by the circumferentialrestraint. The slopes decreased due to the restraint in both in situ andin vitro duodenum and colon, and the intercept decreased due to therestraint in in vitro colon, as shown in Table 1.

As referenced herein, an isovolumic myograph (system 200) was used toassess the role of pressure-induced distension (stretch or strain andtension) on intestinal contractility for both in situ and in vitropreparations and an external restraint was used to separate the effectof distension from pressure. The studies revealed that the intestineremained normally contractile when stretch was induced by intraluminalpressures <10 mmHg. When stretch was induced by the intraluminalpressure of >10 mmHg, intestinal contractility weakened. There was adifferent pattern of contractility from duodenum to colon in response tostretch stimulation. Furthermore, a linear correlation was found betweenintestinal contractility and incremental strain which implicates therole of stretch in intestinal contractility.

The isovolumic myograph may be a useful method to evaluate theintestinal global contractility for understanding the effect ofstimulations of intraluminal pressure on intestinal contraction. Theadvantages of isovolumic myograph to wire and pressure myographs includethe utility to make in situ measurements and application of an externalrestraint (an exemplary device 100 of the present disclosure). Therestraint blocks the distension induced by intraluminal pressure andhence separates the effect of distension from pressure. In fact, theapplication of a restraint in this study limited the increase ofdiameter during inflation as shown in FIGS. 3C and 3D. The restraintattenuated the in situ and in vitro intestinal contractility induced byinflation pressure (shown in FIGS. 5A and 5B), which is consistent withthe prior studies on the pressure-induced contraction of ileum. Thisresult implicates the role of stretch in intestinal contractility.

Further analysis shows that incremental strain plays a stimulatory rolein both in situ and in vitro states through a dose-response relation, asshown in FIGS. 6A and 6B. The restraint attenuates incremental strainand weakened the duodenal and colonic contractility, as shown in FIGS.6C and 6D. Both the slope and intercept were changed by the restraint asdemonstrated in Table 1 for in situlin vitro states and with/withoutrestraint.

Additional studies were performed in connection with the presentdisclosure to determine the effect in body weight by using an exemplarydevice 100 of the present disclosure. A peri-intestinal cuff (exemplarydevice 100) was externally implanted on the proximal duodenum to achievebody weight loss and metabolic restoration. Device 100 was implantedperi-intestinally at 107% larger than the external diameter of duodenumin order not to provide a physical obstruction on the duodenum (so thatdevice 100 was non-constrictive), positioned adjacent to the pyloricsphincter. As noted above, placement of device 100 about the intestine208 decreases the motility of intestine 208. Device 100 reduces thecontractility when chyme pass through and therefore increases thetransit time of the chime, whereby an increased transit time wouldrelate to weight loss and satiety.

Furthermore, use of devices 100 of the present disclosure affectsepithelial function on the duodenum covered under device 100 and henceaffects absorption of nutrients not only at the site of device 100 butbeyond since remodeling (wall thickening) is observed to extend beyondthe site of placement. Intimal thickening occurs with minimal medialsmooth muscle cell damage under an uninterrupted endothelial cell layerwhen one or more devices 100 are placed. The increased thickness mayalso cause nutritional and glucose absorption changes.

FIGS. 8A-9C show food intake, weight loss and blood glucoseconcentration for normal (Wistar, FIGS. 8A-8C) and diabetic (Zuckerdiabetic fatty, FIGS. 9A-9C) rats, respectively. Said figures show acause and effect relation between use of device 100 and foodintake/weight loss where placement cause the decreases and removal causereversal of the effect. As shown in FIGS. 8A-8C, cuff (device 100)implantation reduced body weight and food intake in Wistar rats, andbody weight and food intake were recovered after removal of device 100.FIGS. 9A-9C show reductions in weight, food intake, and plasma glucoselevels in Zucker diabetes fatty rats. Accordingly, use of exemplarydevices 100 of the present disclosure can cause patients to lose weight,decrease food intake/ingestion, and/or reduce blood glucose levels, thelatter being indicative of a treatment for diabetes or another bodilycondition impacted by levels of blood glucose.

FIGS. 10A and 10B show block diagrams of components of exemplary systemsof the present disclosure. As shown in FIG. 10A for example, anexemplary system 1000 (having one or more purposes referenced herein,such as to facilitate weight loss, to facilitate a reduction in foodintake, to treat a blood glucose level condition, etc.) may comprise oneor more devices 100 of the present disclosure and an exemplary deliverydevice 700 of the present disclosure. A second device 100 is shown asoptional in FIG. 10A. Such a system 1000 may have one, two, or moredevices 100. FIG. 10B shows a block diagram of components of anotherexemplary system 1000 of the present disclosure, comprising at least twodevices 100 and an optional delivery device 700. Additional componentsof the present disclosure may also comprise one or more exemplarysystems 1000 of the present disclosure.

In general, and as referenced herein, devices 100 and/or systems 1000can be considered as solutions to various patient problems, such asobesity and diabetes. If a patient is attempting to lose weight, but forwhatever reasons cannot, various devices 100 and/or systems 1000 of thepresent disclosure can solve the patient's problem of not losing weightor problem of being overweight. Similarly, should a patient have aproblem with overeating, have a general excess weight problem not risingto the level of obesity, have a blood glucose problem not rising to thelevel of diabetes, etc., one or more of those problems could be solvedusing various devices 100 and/or systems 1000 of the present disclosure.

Pressure-induced distension has been confirmed as a stimulator ofintestinal afferent sensors. The afferent nerve is excited significantlyin response to inflation, which initiates the sensory transmission tocentral nervous system. Intestinal mechanosensors are located in theintestinal wall, and the increase of pressure in lumen causescontraction of longitudinal muscle of intestine and elicits aperistaltic reflex of intestine where nervous activation is involved.The myogenic response of intestinal smooth muscle and efferentneurogenic contraction are regulated by mechanosensors and entericnerves. The relation between efferent vagus signals and intestinaldistension was identified decades ago. The mechanosensors in intestinalwall are primary sensors of mechanical stimulation. In the studyreferenced herein, the application of an external restraint terminatedthe pressure-induced distension and attenuated the intestinalcontractility, which suggests that stretch or tension but not inflationpressure is the stimulus for intestinal mechanosensors.

The efferent (motor) vagus signals are responses of central nervoussystem to the afferent (sensory) vagus stimulation. Intestinalcontractility is regulated by the extrinsic nervous system(parasympathetic and sympathetic nervous systems) and the intrinsicnervous system. One of the physiological functions of efferent signalsis to regulate the intestinal contractility. Here, in situ and in vitropreparations provided the evidence of nervous regulation. The in vitropreparation implicates the efferent-independent (local regulatory)contraction, in which the efferent nervous signals are interrupted andappear to impact mechanically distension-induced contractility.

Intestinal contractility disorders can arise from intestinal obstructionor ileus. Laparotomy and manipulation also interfere with intestinalmovements. The most widely accepted explanation of postoperative ileusis based on the premise that intestinal manipulation inhibits motorfunction through some neurologic reflex response. Experimental studieshave identified central neural influences that mediate ileus of thegastrointestinal tract. An interesting observation is that the efferentvagus (motor) inactivation may occur after abdominal surgery, e.g.,postoperative intestinal ileus. The intestinal ileus (obstruction) maybe mediated by central neural influences, neurologic reflex (sensitiveafferent nerves) response, the disturbances of myoelectrical activity,humoral responses, and local or regional activation of immune systemfunction. The contractility pattern in response to diameter or pressureas referenced herein may mirror the physical mechanism where surgery orinflammation slows motility of intestine.

The present approach has some limitations that warrant discussion. Theisovolumic condition is non-physiological since it blocks the fluid (orcontent) movement in intestine from oral to anal portions and may affectperistaltic reflex of intestine. An isovolumic myograph only providesthe global but not the local contraction of isolated intestine. Tounderstand the interaction of intestinal nervous activation and smoothmuscle contraction, isovolumic myography must be combined withmeasurements of nervous activation (nervous firing spikes) in additionalstudies. The external restraint may result in ischemia or affect thelymphatic system, albeit it was confirmed that the restraint wasreversible (i.e., function was restored after removal).

The isovolumic myograph 200 may be a component used in a powerful methodto evaluate the intestinal global contractility suitable forunderstanding the effect of stimulations of intraluminal pressure and onintestinal contraction. The regional contraction cannot be measured withthis method and additional approaches are needed to assess localcontraction. An isovolumic condition also blocks the fluid (or content)movement in intestine from oral to anal portions, which may affectperistaltic reflex of intestine. Since this is a non-physiologicalcondition, isovolumic conditions were maintained intermittingly and thenrestored the physiological state. The advantage of isovolumic myographto wire and pressure myographs is the utility to make in situmeasurements

While various embodiments of intestinal devices for facilitating weightloss and methods of using the same have been described in considerabledetail herein, the embodiments are merely offered as non-limitingexamples of the disclosure described herein. It will therefore beunderstood that various changes and modifications may be made, andequivalents may be substituted for elements thereof, without departingfrom the scope of the present disclosure. The present disclosure is notintended to be exhaustive or limiting with respect to the contentthereof.

Further, in describing representative embodiments, the presentdisclosure may have presented a method and/or a process as a particularsequence of steps. However, to the extent that the method or processdoes not rely on the particular order of steps set forth therein, themethod or process should not be limited to the particular sequence ofsteps described, as other sequences of steps may be possible. Therefore,the particular order of the steps disclosed herein should not beconstrued as limitations of the present disclosure. In addition,disclosure directed to a method and/or process should not be limited tothe performance of their steps in the order written. Such sequences maybe varied and still remain within the scope of the present disclosure.

The invention claimed is:
 1. A device, comprising: a first intestinaldevice and a second intestinal device, each defining a longitudinal axisalong its length and each comprising: a body configured for placementaround a portion of an intestine of a patient and further configured toreduce or limit localized intestinal distension and to facilitate weightloss of the patient; and wherein when deployed, the first intestinaldevice is longitudinally adjacent the second intestinal device and aproximal end of the first intestinal device longitudinally overlaps adistal end of the second device.
 2. The device of claim 1, wherein thedevice comprises a temperature-sensitive material so that the device canchange from a first configuration to a second configuration afterplacement of the device within the patient.
 3. The device of claim 1,wherein the body defines an axial gap which defines a 30-45 degree arcof an outer circumference of the body when measured from an oppositeside of the body.
 4. The device of claim 1, wherein the device isconfigured to transform from a compressed, first configuration duringdevice delivery into the patient using a delivery device to anuncompressed, second configuration when the device is within the patientand outside of the delivery device.
 5. The device of claim 1, whereinwhen the device is positioned around the intestine, the device treats adiabetic or other blood glucose level condition of the patient.
 6. Thedevice of claim 1, wherein the body comprises a flexible or pliablematerial.
 7. The device of claim 1, wherein the body comprises abiologically compatible material.
 8. The device of claim 1, wherein thebody has a first, open configuration that can transform to a second,closed or partially closed configuration.
 9. The device of claim 1,wherein the body defines a first end and a second end, and whereinengagement of the first end and the second end effectively closes thedevice.
 10. The device of claim 1, wherein the body is configured forplacement around at least half of a perimeter of the intestine.
 11. Thedevice of claim 1, wherein the body is configured for placementcompletely around the intestine.
 12. The device of claim 1, wherein thebody is sized and shaped so not to invoke any stenosis of the intestinewhen placed around a portion of the intestine.
 13. The device of claim1, wherein the body is sized and shaped so when the device is positionedaround the portion of the intestine, the device does not constrict theintestine.
 14. The device of claim 1, further comprising: a hinged armcoupled to the body at a hinge location; wherein when a hinged arm endengages a relative body end, the device is in a closed configuration;and wherein the device is in an open position when the hinged armextends radially outward.
 15. The device of claim 1, further comprising:a post and a post aperture defined within the body, the post configuredto engage the post aperture to close the device.
 16. The device of claim1, further comprising: one or more tabs positioned at or near a firstend of the body; and a tab receiver positioned at or near a second endof the body, the tab receiver configured to receive the one or more tabsto close the device; wherein the one or more tabs allows a user of thedevice to adjust an overall closed configuration size of the device. 17.A system, comprising: a first intestinal device and a second intestinaldevice, each defining a longitudinal axis along its length andcomprising a body configured for placement around a portion of anintestine of a patient and further configured to reduce or limitlocalized intestinal distension and to facilitate weight loss of thepatient, wherein the first intestinal device is disposed longitudinallyadjacent the second intestinal device and a proximal end of the firstintestinal device longitudinally overlaps a distal end of the seconddevice; a delivery device defining a longitudinal axis along its lengthand configured to receive at least a portion of the first intestinaldevice therein and further configured for at least partial placementinto the patient to deliver the first intestinal device into thepatient; and wherein the first intestinal device and the secondintestinal device are is received in the delivery device such that thelongitudinal axes of the first intestinal device and the secondintestinal device and the longitudinal axis of the delivery device arealigned.
 18. A system, comprising: a first intestinal device and asecond intestinal device, each defining a longitudinal axis along itslength and comprising a body configured for placement around a portionof an intestine of a patient and further configured to reduce or limitlocalized intestinal distension, the system configured to facilitateweight loss of the patient; wherein the first intestinal device and thesecond intestinal device both define an internal diameter; and the firstintestinal device is disposed longitudinally adjacent the secondintestinal device such that a proximal end of the first intestinaldevice at least partially longitudinally overlaps a distal end of thesecond intestinal device.
 19. The system of claim 18, furthercomprising: a delivery device configured to receive at least a portionof the first intestinal device and the second intestinal device thereinand further configured for at least partial placement into the patientto deliver the first intestinal device and the second intestinal deviceinto the patient.
 20. The system of claim 18, wherein the firstintestinal device and the second intestinal device further comprise agenerally circular or elliptical cross section.